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      Microbiomes Detected by Bronchoalveolar Lavage Fluid Metagenomic Next-Generation Sequencing among HIV-Infected and Uninfected Patients with Pulmonary Infection

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          ABSTRACT

          Comparison of lung microbiomes between HIV-infected and uninfected patients with pulmonary infection by metagenomic next-generation sequencing (mNGS) has not been described in China. The lung microbiomes detected in bronchoalveolar fluid (BALF) by mNGS among HIV-infected and uninfected patients with pulmonary infection were reviewed in the First Hospital of Changsha between January 2019 and June 2022. In total, 476 HIV-infected and 280 uninfected patients with pulmonary infection were enrolled. Compared with HIV-uninfected patients, the proportions of Mycobacterium ( P = 0.011), fungi ( P < 0.001), and viruses ( P < 0.001) were significantly higher in HIV-infected patients. The higher positive rate of Mycobacterium tuberculosis (MTB; P = 0.018), higher positive rates of Pneumocystis jirovecii and Talaromyces marneffei (all P < 0.001), and higher positive rate of cytomegalovirus ( P < 0.001) contributed to the increased proportions of Mycobacterium, fungi, and viruses among HIV-infected patients, respectively. The constituent ratios of Streptococcus pneumoniae ( P = 0.007) and Tropheryma whipplei ( P = 0.002) in the bacteria spectrum were significantly higher, while the constituent ratio of Klebsiella pneumoniae ( P = 0.005) was significantly lower in HIV-infected patients than in HIV-uninfected patients. Compared with HIV-uninfected patients, the constituent ratios of P. jirovecii and T. marneffei (all P < 0.001) in the fungal spectrum were significantly higher, while the constituent ratios of Candida and Aspergillus (all P < 0.001) were significantly lower in HIV-infected patients. In comparison to HIV-infected patients without antiretroviral therapy (ART), the proportions of T. whipplei ( P = 0.001), MTB ( P = 0.024), P. jirovecii ( P < 0.001), T. marneffei ( P < 0.001), and cytomegalovirus ( P = 0.008) were significantly lower in HIV-infected patients on ART. Significant differences in lung microbiomes exist between HIV-infected and uninfected patients with pulmonary infection, and ART influences the lung microbiomes among HIV-infected patients with pulmonary infection.

          IMPORTANCE A better understanding of lung microorganisms is conducive to early diagnosis and treatment and will improve the prognosis of HIV-infected patients with pulmonary infection. Currently, few studies have systematically described the spectrum of pulmonary infection among HIV-infected patients. This study is the first to provide comprehensive information on the lung microbiomes of HIV-infected patients with pulmonary infection (as assessed by more sensitive metagenomic next-generation sequencing of bronchoalveolar fluid) compared with those from HIV-uninfected patients, which could provide a reference for the etiology of pulmonary infection among HIV-infected patients.

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          Clinical metagenomics

          Clinical metagenomic next-generation sequencing (mNGS), the comprehensive analysis of microbial and host genetic material (DNA and RNA) in samples from patients, is rapidly moving from research to clinical laboratories. This emerging approach is changing how physicians diagnose and treat infectious disease, with applications spanning a wide range of areas, including antimicrobial resistance, the microbiome, human host gene expression (transcriptomics) and oncology. Here, we focus on the challenges of implementing mNGS in the clinical laboratory and address potential solutions for maximizing its impact on patient care and public health.
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            Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000–15

            Summary Background Pneumococcal conjugate vaccine (PCV) and Haemophilus influenzae type b (Hib) vaccine are now used in most countries. To monitor global and regional progress towards improving child health and to inform national policies for disease prevention and treatment, we prepared global, regional, and national disease burden estimates for these pathogens in children from 2000 to 2015. Methods Using WHO and Maternal and Child Epidemiology Estimation collaboration country-specific estimates of pneumonia and meningitis mortality and pneumonia morbidity from 2000 to 2015, we applied pneumococcal and Hib cause-specific proportions to estimate pathogen-specific deaths and cases. Summary estimates of the proportion of pneumonia deaths and cases attributable to these pathogens were derived from four Hib vaccine and six PCV efficacy and effectiveness study values. The proportion of meningitis deaths due to each pathogen was derived from bacterial meningitis aetiology and adjusted pathogen-specific meningitis case–fatality data. Pneumococcal and Hib meningitis cases were inferred from modelled pathogen-specific meningitis deaths and literature-derived case–fatality estimates. Cases of pneumococcal and Hib syndromes other than pneumonia and meningitis were estimated using the ratio of pathogen-specific non-pneumonia, non-meningitis cases to pathogen-specific meningitis cases from the literature. We accounted for annual HIV infection prevalence, access to care, and vaccine use. Findings We estimated that there were 294 000 pneumococcal deaths (uncertainty range [UR] 192 000–366 000) and 29 500 Hib deaths (18 400–40 700) in HIV-uninfected children aged 1–59 months in 2015. An additional 23 300 deaths (15 300–28 700) associated with pneumococcus and fewer than 1000 deaths associated Hib were estimated to have occurred in children infected with HIV. We estimate that pneumococcal deaths declined by 51% (7–74) and Hib deaths by 90% (78–96) from 2000 to 2015. Most children who died of pneumococcus (81%) and Hib (76%) presented with pneumonia. Less conservative assumptions result in pneumococcccal death estimates that could be as high as 515 000 deaths (302 000–609 000) in 2015. Approximately 50% of all pneumococcal deaths in 2015 occurred in four countries in Africa and Asia: India (68 700 deaths, UR 44 600–86 100), Nigeria (49 000 deaths, 32 400–59 000), the Democratic Republic of the Congo (14 500 deaths, 9300–18 700), and Pakistan (14 400 deaths, 9700–17 000]). India (15 600 deaths, 9800–21 500), Nigeria (3600 deaths, 2200–5100), China (3400 deaths, 2300–4600), and South Sudan (1000 deaths, 600–1400) had the greatest number of Hib deaths in 2015. We estimated 3·7 million episodes (UR 2·7 million–4·3 million) of severe pneumococcus and 340 000 episodes (196 000–669 000) of severe Hib globally in children in 2015. Interpretation The widespread use of Hib vaccine and the recent introduction of PCV in countries with high child mortality is associated with reductions in Hib and pneumococcal cases and deaths. Uncertainties in the burden of pneumococcal disease are largely driven by the fraction of pneumonia deaths attributable to pneumococcus. Progress towards further reducing the global burden of Hib and pneumococcal disease burden will depend on the efforts of a few large countries in Africa and Asia. Funding Bill & Melinda Gates Foundation.
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              Microbiological Diagnostic Performance of Metagenomic Next-generation Sequencing When Applied to Clinical Practice

              Metagenomic next-generation sequencing (mNGS) was suggested to potentially replace traditional microbiological methodology because of its comprehensiveness. However, clinical experience with application of the test is relatively limited.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                Microbiol Spectr
                Microbiol Spectr
                spectrum
                Microbiology Spectrum
                American Society for Microbiology (1752 N St., N.W., Washington, DC )
                2165-0497
                12 July 2023
                Jul-Aug 2023
                12 July 2023
                : 11
                : 4
                : e00005-23
                Affiliations
                [a ] Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China
                [b ] Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, China
                [c ] Department of Infection and Immunology, The First Hospital of Changsha City, Changsha, China
                [d ] Graduate Collaborative Training Base of the First Hospital of Changsha, Hengyang Medical School, University of South China, Hengyang, China
                [e ] Department of Nosocomial Infection Management, Zhongnan Hospital of Wuhan University, Wuhan, China
                [f ] Hubei Engineering Center for Infectious Disease Prevention, Control and Treatment, Wuhan, China
                The University of Auckland
                Author notes

                Yuting Tan, Zhong Chen, and Ziwei Zeng contributed equally to this work. Author order was determined by drawing straws.

                The authors declare no conflict of interest.

                Author information
                https://orcid.org/0000-0002-2332-6172
                https://orcid.org/0000-0003-0490-5328
                Article
                00005-23 spectrum.00005-23
                10.1128/spectrum.00005-23
                10434007
                37436163
                94cf1323-549f-4427-8fb9-a9854ae9e680
                Copyright © 2023 Tan et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

                History
                : 7 January 2023
                : 25 June 2023
                Page count
                supplementary-material: 1, Figures: 5, Tables: 1, Equations: 0, References: 45, Pages: 10, Words: 6248
                Funding
                Funded by: Medical science and Technology Innovation Platform Support Project of Zhongnan Hospital, Wuhan University;
                Award ID: PTXM2020008
                Award Recipient :
                Funded by: Science and Technology Innovation Cultivation Fund of Zhongnan Hospital, Wuhan University;
                Award ID: cxpy2017043
                Award Recipient :
                Funded by: Medical Science Advancement Program (Basic Medical Sciences) of Wuhan University;
                Award ID: TFJC2018004
                Award Recipient :
                Funded by: Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences;
                Award ID: 2020-PT320-004
                Award Recipient :
                Categories
                Research Article
                clinical-microbiology, Clinical Microbiology
                Custom metadata
                July/August 2023

                pulmonary infection,mngs,bronchoalveolar fluid,hiv,human immunodeficiency virus

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